Changes in function of antigen-specific lymphocytes correlating with progression towards diabetes in a transgenic model

The EMBO Journal
Adelaida SarukhanH von Boehmer

Abstract

Mice that express influenza hemagglutinin under control of the rat insulin promoter (INS-HA) as well as a class II major histocompatibility complex (MHC)-restricted HA-specific transgenic TCR (TCR-HA), develop early insulitis with huge infiltrates, but progress late and irregularly to diabetes. Initially, in these mice, INS-HA modulates the reactivity of antigen-specific lymphocytes, such that outside the pancreas they do not cause lethal shock like their naive counterparts in single transgenic TCR-HA mice, when stimulated with high doses of antigen. Inside the pancreas, the antigen-specific cells do not initially attack the islet cells, and produce some IFN-gamma as well as IL-10 and IL-4. Spontaneous progression to diabetes, which can be accelerated by cyclophosphamide injection, is accompanied by a 10-fold increase in IFN-gamma and a 3-fold decrease in IL-10 and IL-4 production by the locally residing antigen-specific T cells. Also, total islets from non-diabetic mice contain more TNF-alpha, compared with diabetic mice. This scenario is consistent with the view that beta cell destruction depends upon the increased production of certain pro-inflammatory cytokines by infiltrating T cells. Our inability to detect Fas expression...Continue Reading

References

Feb 1, 1991·The Journal of Clinical Investigation·I L CampbellL C Harrison
Apr 1, 1991·Journal of Autoimmunity·M Debray-SachsJ F Bach
Feb 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·C O JacobH Acha-Orbea
Mar 1, 1988·European Journal of Immunology·R Yasunami, J F Bach
Dec 1, 1994·European Journal of Immunology·S DegermannD Lo
May 26, 1995·Science·J D KatzD Mathis
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·G S HotamisligilB M Spiegelman
Sep 27, 1993·Journal of Immunological Methods·S L ReinerR M Locksley
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·I AndréD Mathis
Feb 3, 1997·The Journal of Experimental Medicine·A LanoueA Sarukhan
Apr 4, 1997·Cell·A V ChervonskyL A Matis
Aug 18, 1997·The Journal of Experimental Medicine·N ItohY Matsuzawa

❮ Previous
Next ❯

Citations

Dec 14, 2011·Clinical Reviews in Allergy & Immunology·Maria De Santis, Carlo Selmi
Nov 19, 2011·Clinical Reviews in Allergy & Immunology·Matthew F CusickRobert S Fujinami
Feb 28, 2004·Journal of Autoimmunity·Irina Apostolou, Harald Von Boehmer
Mar 24, 2004·Molecular Immunology·Urs Christen, Matthias G von Herrath
Oct 8, 2003·The Journal of Experimental Medicine·Irina ApostolouHarald von Boehmer
Aug 13, 2004·American Journal of Respiratory and Critical Care Medicine·Dunja BruderJan Buer
Jun 1, 2013·Cell Biochemistry and Biophysics·Beatrice Mihaela RaduMihai Radu
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·D L RaduC A Bona
Oct 14, 2008·Expert Opinion on Biological Therapy·Lucy S K Walker
Apr 22, 2010·Drug Discovery Today. Disease Models·T L Van BelleM G von Herrath
Mar 26, 2005·Immunological Reviews·Stephen C L GoughDavid M Sansom
Jan 31, 2006·Seminars in Cancer Biology·Khashayarsha Khazaie, Harald von Boehmer
May 22, 2013·Journal of Diabetes Research·Cathleen PetzoldKarsten Kretschmer
Feb 15, 2005·FEMS Immunology and Medical Microbiology·Astrid M WestendorfDunja Bruder
Feb 28, 2002·Nature Immunology·Sofia CasaresTeodor-Doru Brumeanu
Feb 5, 1999·European Journal of Immunology·I André-SchmutzD Mathis
Jul 17, 2009·Clinical and Vaccine Immunology : CVI·René Segura-VelázquezAdelaida Sarukhan
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucy S K WalkerAbul K Abbas
Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Faiza RharbaouiCarlos A Guzmán
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Craig A ByersdorferEmil R Unanue
Aug 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nadia SarweenLucy S K Walker
Jun 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·N BercoviciR Liblau
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M A SwansonV M Sanders

❮ Previous
Next ❯

Related Concepts

Related Feeds